Low-Dose Vasopressin in the Treatment of Septic Shock in Sheep

Sun, Qinghua; Dimοpoulos, George; Nguyen, Duc Nam; Tu, Zizhi; Nagy, Nathalie; Hoang, Anh Dung; Rogiers, Peter; Backer, Daniel De; Vincent, Jean‐Louis

doi:10.1164/rccm.200205-447oc

Cited by 83 publications

(64 citation statements)

References 35 publications

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“…Sheep in our study were fed a commercial diet containing 7.5 g Na ϩ and 8 g K ϩ /kg. Na ϩ intake was ϳ11 g/day in females and 15 g/day in males, and basal plasma Na ϩ and K ϩ concentrations were in the same range as in other studies (2,49). The acute hypertonic Na ϩ load (0.0275 meq⅐kg Ϫ1 ⅐min Ϫ1 ) administered in this investigation was the equivalent of ϳ20% of normal daily Na ϩ intake (1.65 meq⅐kg Ϫ1 ⅐day…”

supporting

confidence: 65%

Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep

Tang¹,

Carey²,

Bi³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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posure to clinically relevant doses of glucocorticoids during fetal life increases blood pressure in adult male and female sheep. The purpose of this study was to evaluate the effects of prenatal exposure to betamethasone at 80 -81 days of gestation on renal function in ewes and rams at 1.5 yr of age. In prenatal betamethasone-exposed males, compared with the vehicle-exposed animals, basal glomerular filtration rate (GFR) (1.93 Ϯ 0.08 vs. 2.27 Ϯ 0.10 ml ⅐ min Ϫ1 ⅐ kg body wt Ϫ1 ) and the ability to excrete an acute Na ϩ load (37.1 Ϯ 4.4 vs. 53.7 Ϯ 9.7%) were reduced. (P Ͻ 0.03 and P ϭ 0.03, respectively). In contrast, prenatal betamethasone exposure had no effect on basal GFR, Na ϩ excretion, or the percentage of the Na ϩ load excreted during the experiment in females. Systemic infusions of ANG-(1-7) at 9 ng⅐ min Ϫ1 ⅐ kg Ϫ1 for 2 h had minimal effects on basal GFR, renal plasma flow, and Na ϩ excretion in males but increased Na ϩ excretion in females. However, the percentage of Na ϩ load excreted during ANG-(1-7) infusion did not change in prenatal betamethasone-exposed females (113.1 Ϯ 14.2 vs. 98.1 Ϯ 12.2%) compared with the significant increase in vehicle females (139.2 Ϯ 22.3 vs. 92.2 Ϯ 7.5%) (P ϭ 0.01). The data indicate that antenatal betamethasone exposure produces gender-specific alternations in renal function and thus suggest that different mechanisms underlie the antenatal steroid-induced elevations in blood pressure in male and female offspring. prenatal steroid exposure; sodium load; glomerular filtration rate; sodium excretion; angiotensin-(1-7) SINCE ANTENATAL STEROID TREATMENT became the standard of care for enhancing fetal lung maturation in pregnancies threatened by premature labor between 24 and 34 wk of gestation, the use of corticosteroid therapy in the United States has increased from Ͻ15% of eligible pregnancies in 1990 to Ͼ75% in 1995 (1, 3). However, clinical epidemiological studies show an association between antenatal glucocorticoid administration and altered vascular function (7,46), suggesting that exposure to excess glucocorticoids in the prenatal period may have untoward consequences in adult offspring.We and others have shown using sheep and rat experimental models that prenatal steroid exposure results in elevated blood pressure in adulthood (8,10,14,36). Although there are likely multiple targets influencing the effect of steroids on blood pressure, several recent studies have suggested that altered kidney development induced by antenatal glucocorticoids may contribute to the elevations in arterial blood pressure (35,36,53). It is well known that the kidneys play a major role in the long-term regulation of arterial pressure and that change in renal function may lead to alterations in Na ϩ and water balance and blood pressure (19). In a rat model, Ortiz et al. (35,36) observed that prenatal exposure to dexamethasone on days 15 and 16 of gestation induced 30 and 20% reductions in glomerular number in offspring compared with controls when assessed at 60 -70 days and 6 -9 mo of age, ...

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supporting

confidence: 65%

Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep

Tang¹,

Carey²,

Bi³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Sun et al (27) demonstrated that some advantages of AVP use are mainly observed after 16 h. Our data clearly demonstrate the acute effects of AVP in hypotensive normodynamic shock but cannot be extrapolated for a longer period. This limitation could also explain the lack of histological lesions.…”

Section: Limitations Of Studycontrasting

confidence: 51%

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Lévy

Vallée²,

Lauzier³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Comparative effects of vasopressin, norepinephrine, and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock. Am J Physiol Heart Circ Physiol 287: H209 -H215, 2004. First published February 26, 2004 10.1152/ajpheart.00946.2003, a standard of care, AVP, an alternative candidate, and L-canavanine (LC), a selective inhibitor of inducible nitric oxide synthase, were compared for efficacy and innocuousness on global and regional hemodynamics, plasmatic and tissue lactate-to-pyruvate ratio (L/P), tissue high-energy phosphates, renal function, and tissue capillary permeability in a rat model of endotoxic normokinetic shock. Mean arterial pressure (MAP) decreased (ϳ35%) but aortic blood flow increased during endotoxin infusion (P Ͻ 0.05 vs. control). Additionally, there was a decrease in mesenteric (MBF) and renal (RBF) blood flows along with regional-to-systemic ratio (P Ͻ 0.05 vs. control). All tested drugs restored MAP to basal levels but slightly decreased abdominal aortic flow; however, RBF and MBF remained unchanged. Endotoxin significantly decreased diuresis and inulin clearance (ϳ3-to 4-fold), whereas AVP or LC attenuated this drop (P Ͻ 0.05 vs. control). In contrast, NE did not improve endotoxininduced renal dysfunction. Endotoxin induced gut and lung hyperpermeability (P Ͻ 0.05 vs. control). Endotoxin-induced gut hyperpermeability was inhibited by AVP, LC, and NE. Endotoxin-induced lung hyperpermeability was further worsened by NE (ϳ2-fold increase) but not AVP infusion (P Ͻ 0.05 vs. endotoxin). LC significantly improved endotoxin-induced pulmonary hyperpermeability. Endotoxin increased renal lactate and decreased renal ATP. NE did not change renal lactate or renal ATP. AVP and LC decreased renal lactate and normalized renal ATP. Finally, endotoxin was associated with increased lactate levels and L/P (ϳ2-and 1.5-fold increases vs. control, respectively), whereas AVP and LC, but not NE, normalized both parameters after endotoxin challenge. These results suggest that, in a short-term endotoxic shock model, AVP improves systemic hemodynamics without side effects and has particular beneficial effects on renal function. septic shock; vascular permeability; renal function THE HUMAN RESPONSE to septic challenge usually includes increased cardiac output, decreased peripheral resistance, low arterial pressure, and increased vascular permeability. AVP, also known as "the" antidiuretic hormone (ADH), is an emerging alternative candidate for management of redistributive shock (7). Indeed, AVP exhibits strong vasoconstrictor effects through stimulation of the V1 receptor leading to arterial pressure improvement (28). Moreover, low concentrations of exogenous AVP mediate vasodilatation in coronary, cerebral, and pulmonary arterial circulation (20). The recognized effects of AVP on renal function are complex and include association of an antidiuretic effect through stimulation of V2 receptors, an increase of diuresis/natriuresis through V1 receptors by efferent arteriolar vasoconstric...

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“…In a rodent endotoxin model, both NE-and AVP-treated rats demonstrated better preservation of gut permeability in comparison to control animals, as measured by Evans Blue tissue concentration. 35 Sun et al 36 also reported that sheep undergoing cecal perforation exhibit less small intestinal edema and congestion when exposed to combined AVP and NE in lieu of NE alone.…”

Section: Impact Of Ne and Avp On Intestinal Function In The Septic Pamentioning

confidence: 97%

“…On the other hand, other presently unidentified or lesser known AVP-dependent receptors (i.e., vasopressinactivated calcium-mobilizing receptor) may eventually be discovered or better characterized. 36 In addition, AVP could function with the salt pump sodium epithelial channel whose expression is enhanced in the lung of AVP-sustained exposed rats. 37 Other mechanisms by which AVP can be protective may possibly include AVP-induced atrial natriuretic peptide secretion, via the vasopressin-3 receptor, which can attenuate lung permeability.…”

Section: Impact Of Ne and Avp On Pulmonary Function And Vascular Permmentioning

confidence: 99%

Review article: Organ per fusion/permeabilityrelated effects of norepinephrine and vasopressin in sepsis

Farand¹,

Hamel

Lauzier

et al. 2006

Can J Anesth/J Can Anesth

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Purpose:One invariable hallmark of severe sepsis is generalized tissue "malperfusion" and hyperpermeability secondary to microcirculatory/capillary leakage. This review focuses on direct and/or indirect influences of norepinephrine, as a standard of care, and vasopressin, as an alternative vasoactive drug, on organ and tissue perfusion/permeability in severe sepsis.Source: English and French language articles and books published between 1966 and 2005 were identified through a computerized Medline search using the terms "sepsis, permeability, norepinephrine and vasopressin". Relevant publications were retrieved and scanned for additional sources. Principal findings:There are few randomized clinical trials comparing different vasopressors in sepsis; most available literature consists of clinical reports, animal experiments and occasional reviews. Based on the best current evidence from these sources, we describe the status of major organ perfusion/ permeability in sepsis (i.e., the lung, the kidney, the heart, the intestine/gut) in the context of sepsis-induced organ dysfunction/failure. Potential and differential therapeutic effects of the vasopressors norepinephrine and arginine-vasopressin, in the setting of sepsis, are identified. Conclusions:In the treatment of sepsis, arginine-vasopressin exhibits organ-specific heterogeneity in vascular responsiveness, compared to norepinephrine. While norepinephrine is a current standard of care in sepsis, arginine-vasopressin shows promise for the treatment of septic shock. Objectif

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Low-Dose Vasopressin in the Treatment of Septic Shock in Sheep

Cited by 83 publications

References 35 publications

Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep

Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Review article: Organ per fusion/permeabilityrelated effects of norepinephrine and vasopressin in sepsis

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